Hybrid resistance to parental NZW bone marrow grafts: association with the D end of H-2.

Abstract

F1 hybrid and allogeneic mice of several strains rejected NZW bone marrow grafts even though the cell transfer was preceded by an acute and lethal exposure to γ-irradiation. Mice of these strains were designated “resistant.” F1 and inbred mice of other strains did not reject NZW grafts and were designated “susceptible.” Interstrain variation in the ability to reject parental or allogeneic NZW grafts was observed even when H-2 differences between hosts and donor were kept identical. Maturation of resistance did, not occur until the 5th week of life in (NZW × NZB)F1 hybrids. In adults, resistance was weakened or abrogated by administration of cyclophosphamide and by sublethal exposure to γ-rays 14 days prior to a second exposure and transplantation. The frequency of resistant and susceptible animals in segregating progeny of (NZW × NZB)F1 hybrids backcrossed to NZW mice was compatible with genetic control by a single autosomal locus closely associated with H-2 in linkage group IX. The genetic determinant of hybrid resistance to NZW grafts was mapped in or near the D end of H-2 by testing F1 hybrids from NZW parents outcrossed to mice congenic with strain B10 and/or carrying recombinant H-2 alleles. The locus is presumably identical to Hh-1 responsible for hybrid resistance to B10 and other inbred strain marrow grafts. In conclusion, hemopoietic grafts of NZW donors were the targets of a transplantation reaction in heavily irradiated host mice. Peculiar features were the parent to F1 hybrid incompatibility, the persistence of reactivity after acute irradiation of prospective hosts, and the additional regulation of reactivity by genetic factors other than the primary determinants of transplantation antigens.